The research proposals described in this application are designed to elucidate the control of RNA and protein synthesis and the intracellular processing or secretion of newly synthesized proteins in certain mature mammalian tissues, to assess the role of development in the establishment of such processes and to relate events occurring during fetal or early postnatal life to those found in maturity. Since it is clear that protein synthesis may be under both gene-regulated and non-genetic exogenous control, emphasis will be placed not only on protein synthesis, but also on intracellular events triggered by hormones, neurohumoral transmitters and such factors as diet, fasting and drugs. Two models are under investigation in this laboratory. Each is characterized by active protein synthesis and also by highly organized but different mechanisms for the intracellular processing of newly synthesized proteins. Both models concern areas of central importance in gastrointestinal function in fetal and early life as well as in maturity and work in both areas serves to contrast and compare the 2 models; 1. Development and control of intestinal membrane function and of the intracellular processing of disaccharidases; 2. Development and control of secretion and synthesis of enzymes in exocrine glands. Studies will be performed to measure the rates of synthesis of intestinal sucrase under a variety of experimental conditions and during development using immunochemical methods and monospecific antibody to rat sucrase. RNA synthesis will also be studied in order to evaluate transcriptional control of sucrase synthesis. Experiments will be performed to elucidate intracellular mechanisms controlling secretion in exocrine glands. Tissue levels of cyclic nucleotides (cGMP and cAMP) will be measured after exposure of glands to autonomic stimuli, GI hormones and their antagonists, in a short term organ culture system. Factors controlling binding of agents to membranes will be analyzed, as well as triggering events effecting secretion.